PubMed Health⌕ Search

Biomedical subjects

B Sherman

Publications and source records attributed to B Sherman.

At least 55 records · Page 3Linked to original sources

Circadian analysis of plasma cortisol levels before and after dexamethasone administration in depressed patients.

Pituitary-adrenal regulation in healthy subjects and in depressed patients is very dynamic. Interpretation of results of the 1-mg dexamethasone suppression test has usually depended on the result of a single blood cortisol level measurement obtained in the morning or afternoon. We analyzed circulating cortisol concentrations by obtaining blood samples at 20-minute intervals for 24 hours before and after dexamethasone administration in depressed patients. The results illustrate the variability in patterns of escape from the effects of dexamethasone among depressed patients; they also indicate the influence of the sampling time on the test results and thus on the relationship of the test result to various clinical classifications. Finally, these results provide the basis for understanding the consequences of alternative sampling strategies.

Circadian Rhythm↗

Characterization of a cytosolic steroid-binding protein in the liver of the winter flounder, Pseudopleuronectes americanus.

The winter flounder liver contains significant concentrations of estrogen binding protein(s) that fulfill some of the criteria normally assigned to receptor proteins, in that these proteins are saturated at low substrate concentrations (less than 5 nM) and have a high affinity for ligand (Kd approximately 6 X 10(-10) M for [3H]17 beta-estradiol). Sedimentation analysis of the 17 beta-estradiol-binding protein complex on 5-20% sucrose density gradients detected an 8 S form of the binding protein under low salt conditions. Nonspecific sites sedimented in the 4 S region. These sedimentation characteristics are similar to those observed for the estrogen receptor and nonspecific binding sites in mammalian tissues. In contrast to mammalian estrogen receptor, which binds selectively to estrogens, the binding protein(s) investigated in our studies also binds other steroids. Competitive binding studies demonstrated that 10-fold excess of unlabeled testosterone and progesterone displaced 50 and 45% of [3H]17 beta-estradiol from the binding protein, respectively. These studies demonstrate the presence of steroid-binding protein in liver of female winter flounder which might play a role in regulating hepatic steroid hormone action.

Animals↗

Platelet and fibroblast monoamine oxidase in alcoholism.

Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.

Alcoholism↗

Estrogen use and breast cancer. Interaction with body mass.

With few exceptions, most epidemiologic studies do not show an excess relative risk of breast cancer associated with menopausal estrogen therapy. Other studies show a relationship of breast cancer to obesity, which is characterized by increased endogenous estrogen production. This study explored the possibility of an interaction between ponderosity and exogenous estrogen use in a case-control study of 113 postmenopausal breast cancer patients and pair-matched hospital control subjects. In this series, neither menopausal estrogen use nor relative weight were significantly associated with breast cancer risk. However, among estrogen users, the relative risk of breast cancer was strikingly influenced by the ponderosity of the subjects; the relative risk was 0.41 for women whose relative weight was less than the median, compared with 1.29 for those whose relative weight exceeded the median. The mean age was also examined at diagnosis in order to explore the potential of exogenous estrogen as a tumor promotor. The mean age at breast cancer diagnosis in estrogen users, 58.1 years, was significantly lower than in nonusers, 63 years. A significant linear relationship was found between age at diagnosis and body weight among estrogen users. Estrogen-treated women in the lowest tertile of body weight had the diagnosis of breast cancer made seven years earlier than those in the highest tertile of weight. There was no significant difference in the distribution of clinical stages at diagnosis between estrogen users and nonusers. These data suggest that relative body weight is an important modifier of the effect of exogenous estrogens on breast cancer biology.

Age Factors↗

Bone density in amenorrheic women with and without hyperprolactinemia.

To determine whether decreased bone density in patients with PRL-secreting pituitary tumors is specifically related to hyperprolactinemia or is a consequence of disordered pituitary-gonadal function common to all amenorrheic states, we measured the bone mineral content of the radius by photon absorptiometry in normal subjects, in women with amenorrhea and normal serum PRL levels, and in women with PRL-secreting pituitary tumors. The women did not differ significantly in mean age, height, weight, or serum calcium, phosphorous, gonadotropin, testosterone, vitamin D, or PTH concentrations, and all had normal renal and thyroid function. The bone mineral content in women with amenorrhea and normal serum PRL levels (0.91 +/- 0.02 g/cm) was not significantly different from that in control subjects (0.88 +/- 0.01 g/cm). Patients with PRL-secreting tumors studied 2-5 yr after transsphenoidal surgery had significantly diminished bone mineral content whether they were cured (0.82 +/- 0.02 g/cm) or had persistent amenorrhea and hyperprolactinemia (0.81 +/- 0.02 g/cm). Serum estradiol concentrations did not differ significantly in the four groups, and there was no correlation between estradiol concentration and bone mineral content or between PRL concentration and bone mineral content in the amenorrheic women. The presence of decreased bone mineral content in hyperprolactinemic patients suggests that PRL may have a direct effect on bone and may be another indication for early treatment of PRL-secreting pituitary tumors.

Adult↗

Further studies of the effects of inhaled glucocorticoids on pituitary-adrenal function in healthy adults.

We compared the effects of increasing doses of beclomethasone dipropionate (BDP) and fluocortin butylester (FCB) on several indices of pituitary-adrenal function in healthy adult subjects. Significant depression of urinary free cortisol excretion and the response to metyrapone was seen only at the highest dose (1600 mg/day) of BDP. This depression was not reflected by frequent measurement of the serum cortisol concentration. FCB used well in excess of its presumed therapeutic dose range showed no evidence of any effect on pituitary-adrenal function. These results confirm that at high doses BDP causes pituitary adrenal suppression. Differences from studies showing reduced adrenal function in children on BDP doses of 400 to 800 mg/day probably reflect differences in the dose per kilogram of body weight. Since the use of FCB was not accompanied by any adverse side effects or evidence of reduced pituitary-adrenal function, it may be a variable alternative for asthmatics who require high doses of inhaled glucocorticoid.

Administration, Intranasal↗

A combined in vivo/in vitro study of the presynaptic release of adenosine derivatives in the hippocampus.

To investigate the release of adenine compounds from defined neuronal pathways, we employed a hippocampal slice preparation in which a selective-loading of the releasable pools was achieved in vivo with the aid of axonal transport. By injecting radioactive adenosine stereotaxically into the entorhinal cortex, the major afferent system to the dentate gyrus (the perforant path) was loaded within 20-36 h, at which time the rats were killed and hippocampal slices were prepared. The efflux of radioactive material, as recovered from the perfusate and measured in a scintillation counter, was found to be significantly increased in response to electrophysiologically controlled stimulation of the perforant path but not to stimulation of an alternative fiber tract, the fimbria. These findings provide supportive and more direct evidence for an activation-coupled release of adenosine derivatives from presynaptic sites in the central nervous system.

Adenosine↗

Ions and water in the epithelial cells of rabbit descending colon.

1. Isolated sheets of rabbit descending colon epithelial cells stripped from their underlying muscle coats were incubated in chambers at 37 degrees C with oxygenated media, and their non-inulin space water, sodium, potassium and chloride contents were subsequently determined. 2. With sodium Ringer bathing both surfaces, amiloride, 10(-4) M, decreased non-inulin space sodium content by 76 mmol/kg dry wt. Ouabain, 10(-3) M, caused loss of non-inulin space potassium which was not completely compensated for by uptake of sodium over 30 min incubation. Chloride and water, therefore, decreased. Amiloride, 10(-4) M, inhibited but did not prevent this uptake of sodium after ouabain. 3. Tissues exposed to sodium-free choline Ringer rapidly exchanged non-inulin space sodium for choline and, more slowly, lost potassium, chloride and water. The equilibration of sodium in the non-inulin space when sodium Ringer was restored to the mucosal medium alone was largely amiloride-insensitive. For restoration of non-inulin space potassium to normal levels, sodium was required in the serosal but not the mucosal medium. 4. Neither the absence of glucose nor the absence of chloride from the mucosal medium affected the non-inulin space sodium content when sodium was restored to the mucosal medium bathing sodium-depleted tissues. 5. It is argued that, whereas non-inulin space potassium and water contents are synonymous with their cellular values, only about one third of non-inulin space sodium is cellular when sodium Ringer bathes both surfaces, and the concentration of the sodium within the cellular transport pool approximated 20 mmol/kg H2O, consistent with estimates obtained from other techniques.

Amiloride↗

Structural responses to voltage-clamping in the toad urinary bladder. II. Granular cells and the natriferic action of vasopressin.

The natriferic action of vasopressin has been investigated with morphological studies of voltage-clamped toad urinary bladders. Granular cell swelling can be induced in the presence of isoosmotic solutions when the orientation of the transmural potential is reversed by voltage clamping (V.A. Bobrycki, J. W. Mills, A.D.C. Macknight & D. R. DiBona, J. Membrane Biol., 60:21, 1981) and results from an increased rate of sodium entry across the mucosal membrane; under these conditions the active transport mechanism at the basal-lateral membrane becomes rate-limiting. Vasopressin exacerbated the voltage-reversal-induced swelling of granular cells while other cell types were unaffected. Granular cell swelling appeared to be dependent upon sodium entry from the mucosal medium since it was completely prevented by amiloride. There was no evidence for an effect of vasopressin on tight junction permeability; voltage-reversal induced the same amount of junction blistering whether or not vasopressin was present. It is concluded that the predominant effect of vasopressin on transepithelial sodium transport is to increase the sodium conductance of the mucosal plasma membrane. As is the case with the hydroosmotic effect of the hormone, the natriferic action of vasopressin seems to be exerted primarily, if not entirely, on the granular cells.

Amiloride↗

Relationship of body weight to menarcheal and menopausal age: implications for breast cancer risk.

Early menarche and late menopause are risk factors for the development of breast cancer. An adequate hormonal mechanism for those observations has not been described. Because obesity has also been associated with increased breast cancer risk, we examined the relationship among height, weight, adiposity, and menstrual cycle characteristics in women who prospectively recorded menstrual cycle intervals and reproductive events as part of the Menstrual and Reproductive History Research Program. Within this study cohort, adult height, weight, and a derived index of adiposity were related to both earlier age at menarche and later age at menopause. The association of early age at menarche with adiposity persisted from age 18 yr through middle age and into the menopausal years. There was no relationship between body mass and age at first pregnancy, another breast cancer risk factor. Women who were heavier at 18 yr of age and thereafter gained 5 lb or more had significantly greater mean menstrual cycle length and variability during the 7-yr period after menarche than the other members of the cohort. There was no obvious relationship between weight indices and menstrual cycle pattern during mature reproductive life or during the 7 yr before menopause. Our data suggest that menarcheal and menopausal age may have a common relationship to nutritional status and to constitutional features that predate the onset of menarche and persist into later life.

Adipose Tissue↗

Predictors of the outcome of transsphenoidal surgery for prolactin-secreting pituitary adenomas.

Sixty-seven women who underwent transsphenoidal resection of PRL-secreting pituitary adenomas between 1976 and 1979 were separated into categories according to the manner of their clinical presentation. Forty-one had oral contraceptive-related onset of amenorrhea-galactorrhea, 5 had pregnancy-related onset of amenorrhea-galactorrhea, 5 had primary amenorrhea, and 16 had the spontaneous onset of amenorrhea-galactorrhea unrelated to estrogen use. Surgical success, defined as the resumption of regular menses and normalization of serum PRL concentration, was achieved in 54% of those with estrogen-related onset of amenorrhea-galactorrhea compared with 19% in the other group. The analysis of multiple preoperative features, including clinical classification, age, preoperative PRL concentration, and duration of amenorrhea-galactorrhea by logistic regression, demonstrated that the clinical classification was the most important factor in predicting the outcome of transsphenoidal surgery. It should be a prime consideration in the selection of therapy for PRL-secreting adenomas.

Adenoma↗

1-phenylalanine mustard (L-PAM) in the management of premenopausal patients with primary breast cancer: lack of association of disease-free survival with depression of ovarian function. National Surgical Adjuvant Project for Breast and Bowel Cancers.

Breast cancer patients participating in a prospective randomized clinical trial who were less than or equal to 49 years of age, had positive axillary nodes, and who received prolonged 1-phenylalanine mustard (L-PAM) as an adjuvant to mastectomy continue (after 4 years) to demonstrate a significantly greater disease-free survival (p = .007) than do patients who received placebo. Benefit was achieved in patients who were less than or equal to 39 years as well as those who were 40-49 years of age. Those in the younger age group showed a greater improvement in disease-free survival at 4 years relative to their controls (32% vs. 69%; p = .01) than did those in the older age group (48% vs. 61%; p = .09). When patients were examined relative to their nodal status, a highly favorable effect was found to have been achieved with L-PAM in those with 1-3 positive nodes (54% vs. 86%; p = .006). Results indicate that both age groups were benefited. When considered over time, they demonstrate that a relatively greater effect was achieved in the younger women. While L-PAM failed to significantly alter the disease-free survival of those with greater than or equal to 4 positive nodes a slightly better effect was achieved in the group less than or equal to 39 years. Since adjuvant chemotherapy has been found to be more effective in premenopausal than postmenopausal women, it has been presumed that decreased ovarian function, as a result of the chemotherapy, is responsible for the findings. To support or repudiate that concept, information regarding serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), as well as menstrual function, has been obtained from women receiving L-PAM or L-PAM plus 5-FU therapy. In contrast to findings relative to disease-free survival, ovarian function and menses were most affected in patients 40-49 years of age. Amenorrhea occurred in 73% of patients in that age group and in only 22% of those less than or equal to 39 years (p less than .001). Similarly, a significant increase in LH and FSH and a decrease in E2, all indicative of ovarian suppression, was observed only in the older group of patients. Thus, it is concluded that while ovarian suppression may account for some of the adjuvant chemotherapeutic effect in premenopausal women, the dichotomy of findings in younger and older premenopausal women relative to therapeutic response and ovarian function indicates that other factors could be responsible.

Adult↗

Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma.

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.

Administration, Oral↗